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Interferon gamma induces differential upregulation of alpha and beta chemokine secretion in colonic epithelial cell lines

Interferon gamma induces differential upregulation of alpha and beta chemokine secretion in colonic epithelial cell lines

Gut 42(2): 208-213

Background-Production of chemoattractant factors by the intestinal epithelium may contribute to mucosal infiltration by inflammatory cells in inflammatory bowel disease. Secretion of the alpha chemokine interleukin 8 (IL-8), a neutrophil chemoattractant, has been widely studied, but little is known about epithelial secretion of beta chemokines, which are preferentially involved in recruiting monocytes. Aims-To investigate the profiles of alpha and beta chemokine secretion in colonic cell lines and their differential modulation by interferon gamma (IFN-gamma), a product of activated T lymphocytes and natural killer cells. Methods and results-HT29-19A, a model of the Cl- secretory crypt cell, exhibited a parallel secretion of the a chemokines IL-8 and GROalpha, which could be markedly upregulated by tumour necrosis factor alpha (TNF-alpha) and IL-1beta. These cells showed no significant expression of the beta chemokines RANTES (regulated upon activation T cell expressed and secreted), MIP-1alpha (macrophage inflammatory protein 1alpha), and MCP-1 (monocyte chemotactic protein 1) under these conditions, but IFN-gamma in combination with TNF-alpha caused a dose dependent induction of RANTES and MCP-1 secretion. This was accompanied by a marked increase of RANTES mRNA. In contrast, IFN-gamma had no significant effect on TNF-alpha stimulated IL-8 secretion. Caco-2 cells, with features more typical of villus absorptive cells, were relatively poor secretors of alpha chemokines but secreted high levels of MCP-1 in response to IL-1beta. IFN-gamma did not influence alpha or beta chemokine secretion in these cells. Conclusions-These studies suggest that intestinal epithelial cells may produce chemokines capable of attracting both neutrophils and monocytes. The ability of IFN-gamma to activate the expression of beta chemokines preferentially could facilitate the development of chronic inflammatory infiltrates.

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Accession: 008896468

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PMID: 9536945

DOI: 10.1136/gut.42.2.208

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